Download Project Leader Contact Information

Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
PhUSE
PhUSE Computational Science Standard
Analyses and Code Sharing Working Group
Script Discovery and Acquisition Project Team
Screen Shots of the Displays Created by JumpStart
Programs
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
1
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
Table of Contents
1.
Disclaimer ........................................................................................................................... 3
2.
Notice of Current Edition ..................................................................................................... 3
3.
Additions and/or Revisions .................................................................................................. 3
4.
Purpose .............................................................................................................................. 3
5.
Acknowledgements ............................................................................................................. 4
6.
Project Leader Contact Information ..................................................................................... 4
7.
References ......................................................................................................................... 4
8.
Appendices ......................................................................................................................... 5
8.1.
AE Severity .................................................................................................................. 5
8.2.
AE Toxicity ..................................................................................................................13
8.3.
Demographics.............................................................................................................18
8.4.
Disposition ..................................................................................................................23
8.5.
Exposure ....................................................................................................................26
8.6.
Liver ............................................................................................................................31
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
2
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
1.
Disclaimer
The opinions expressed in this document are those of the authors and do not necessarily
represent the opinions of the Pharmaceuticals User Software Exchange (PhUSE), members'
respective companies or organizations, or regulatory authorities. The content in this document
should not be interpreted as a data standard and/or information required by regulatory authorities.
2.
Notice of Current Edition
This edition of the “Screen Shots of the Displays Created by JumpStart Programs” white paper is
the first edition.
3.
Additions and/or Revisions
Date
Author
Version
Changes
2017-Mar-17
See Section 5
v1.0
First edition
4.
Purpose
The purpose of this document is to show the displays that are created when the FDA utilizes their
JumpStart service when receiving clinical trial data as part of a submission. As noted on Food
and Drug Administration’s (FDA’s) web site [1], JumpStart runs a series of drug clinical trial
data analyses early in the review process to assess data composition, quality, analyses options,
and tools for the analyses, so reviewers have a better understanding of the data and have the
information to conduct an effective evaluation of the drug submission. JumpStart provides these
data findings to the reviewers shortly after the receipt of a new submission, giving reviewers
time to clarify issues or make requests of the organizations developing the drug before
proceeding in the review process. JumpStart also provides data analyses that highlight areas of
concern and may warrant further attention. For additional information on JumpStart including
what it is, its benefits, and how it works, visit the FDA’s web site [1].
The displays provided here are not necessarily consistent with regulatory guidance documents or
white papers created by the PhUSE Analysis and Display White Papers (ADW) Project Team.
We do not recommend that sponsors create these tables and figures instead of those already in a
sponsor’s standards library or those that are recommended by the PhUSE ADW project team.
Instead, these displays inform sponsors of what the FDA will likely see early in their review
process. Updates or modifications to a sponsor’s standards may be warranted if conceptual gaps
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
3
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
are identified. However, sponsors may want to run the JumpStart scripts to ensure the FDA will
be able to run them without errors. The FDA shared their JumpStart scripts with the PhUSE
Script Repository Discovery and Acquisition Project Team and the scripts have been uploaded to
the PhUSE Script Repository in GitHub [2].
If interested in ensuring the FDA will be able to run the JumpStart scripts without errors or in
duplicating the displays, sponsors can start with and access the codes provided in the PhUSE
Script Repository in GitHub by following these links:



5.
Index of all scripts: https://github.com/phuse-org/phuse-scripts/wiki/Simple-Index
Index of FDA JumpStart Scripts: https://github.com/phuse-org/phusescripts/wiki/JumpStart-Scripts.
Once a script is tested, it will be in the tested/SAS folder
Acknowledgements
The primary contributors include Rebeka Revis, Hamning Tu, Mary Nilsson, and Ted Peterson.
Thank you to Casie Polanco for editorial support. Thank you to all the original authors of the
JumpStart scripts and those involved with updates to the scripts over time.
6.
Project Leader Contact Information
Rebeka Revis
Eli Lilly & Company
Indianapolis, IN 46285
Work Phone: (317) 503-6480
E-mail: [email protected]
7.
References
1. JumpStarting Drug Review. Food and Drug Administration web site. Available at:
https://www.fda.gov/Drugs/ResourcesForYou/Consumers/ucm397921.htm. Accessed 13
Feb 2017.
2. Slain J, Tu H. CS07: Get a Jump Start on Clinical Data Analysis and Visualization with
Standard Scripts. PhUSE Wiki. Available at:
http://www.phusewiki.org/docs/Conference%202016%20CS%20Paper/CS07.pdf.
Accessed 13 Feb 2017.
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
4
Project: Script Discovery and Acquisition Project Team
Working Group: Standard
Analyses and Code Sharing
Title: Screen Shots of the Displays Created by JumpStart Programs
8.
Appendices
8.1. AE Severity
Analysis 1: Adverse Events by Arm Greater than 2%
Adverse Events by Organ Class and Term
NDA/BLA: 12345
Study: 123
Analysis run date: 2015-03-11 11:22:04 AM
Where subject count is the number of subjects in the treatment arm experiencing at least one adverse event per organ
class and term and greater than 2% of subjects in any arm experienced at least one adverse event
Placebo
Body System or Organ Class
Dictionary-Derived Term
N=577
Subject
Count
Blood And Lymphatic System Disorders
Blood And Lymphatic System Disorders
Cardiac Disorders
Cardiac Disorders
Cardiac Disorders
Ear And Labyrinth Disorders
Endocrine Disorders
Gastrointestinal Disorders
Gastrointestinal Disorders
Gastrointestinal Disorders
Gastrointestinal Disorders
Gastrointestinal Disorders
Gastrointestinal Disorders
Gastrointestinal Disorders
Gastrointestinal Disorders
Treatment
Anaemia
Iron Deficiency Anaemia
Right Ventricular Failure
Palpitations
Atrial Fibrillation
Vertigo
Hypothyroidism
Diarrhoea
Nausea
Vomiting
Abdominal Pain
Abdominal Pain Upper
Abdominal Distension
Dyspepsia
Abdominal Discomfort
31
15
59
32
11
10
12
107
104
50
32
32
23
14
14
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
5
Total
N=575
%
5.4
2.6
10.2
5.5
1.9
1.7
2.1
18.5
18.0
8.7
5.5
5.5
4.0
2.4
2.4
Subject
Count
48
5
45
34
12
15
8
243
191
103
48
34
18
24
21
N=1,152
%
8.3
0.9
7.8
5.9
2.1
2.6
1.4
42.3
33.2
17.9
8.3
5.9
3.1
4.2
3.7
Subject
Count
79
20
104
66
23
25
20
350
295
153
80
66
41
38
35
%
6.9
1.7
9.0
5.7
2.0
2.2
1.7
30.4
25.6
13.3
6.9
5.7
3.6
3.3
3.0
Project: Script Discovery and Acquisition Project Team
Working Group: Standard
Analyses and Code Sharing
Title: Screen Shots of the Displays Created by JumpStart Programs
Analysis 2: Serious Adverse Events by Arm
Serious Adverse Events by Organ Class and Term
NDA/BLA: 12345
Study: 123
Analysis run date: 2015-03-11 11:22:04 AM
Where subject count is the number of subjects in the treatment arm experiencing at least one serious adverse event per
organ class and term
Placebo
Body System or Organ Class
Dictionary-Derived Term
N=577
Subject
Count
Blood And Lymphatic System
Blood And Lymphatic System
Blood And Lymphatic System
Blood And Lymphatic System
Blood And Lymphatic System
Blood And Lymphatic System
Cardiac Disorders
Cardiac Disorders
Cardiac Disorders
Cardiac Disorders
Cardiac Disorders
Cardiac Disorders
Cardiac Disorders
Cardiac Disorders
Cardiac Disorders
Disorders
Disorders
Disorders
Disorders
Disorders
Disorders
Treatment
Anaemia
Haemorrhagic Anaemia
Idiopathic Thrombocytopenic Purpura
Leukopenia
Neutropenia
Thrombocytopenia
Right Ventricular Failure
Atrial Fibrillation
Atrial Flutter
Acute Right Ventricular Failure
Cardiac Arrest
Supraventricular Tachycardia
Cardio-Respiratory Arrest
Cardiogenic Shock
Cardiopulmonary Failure
3
0
0
0
1
0
42
4
4
5
4
4
2
2
1
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
6
Total
N=575
%
0.5
0.0
0.0
0.0
0.2
0.0
7.3
0.7
0.7
0.9
0.7
0.7
0.3
0.3
0.2
Subject
Count
5
1
1
1
0
1
34
7
4
2
2
1
2
2
3
N=1,152
%
0.9
0.2
0.2
0.2
0.0
0.2
5.9
1.2
0.7
0.3
0.3
0.2
0.3
0.3
0.5
Subject
Count
8
1
1
1
1
1
76
11
8
7
6
5
4
4
4
%
0.7
0.1
0.1
0.1
0.1
0.1
6.6
1.0
0.7
0.6
0.5
0.4
0.3
0.3
0.3
Project: Script Discovery and Acquisition Project Team
Working Group: Standard
Analyses and Code Sharing
Title: Screen Shots of the Displays Created by JumpStart Programs
Analysis 3: Adverse Events by Severity and Arm
Adverse Events by Severity Level
NDA/BLA: 12345
Study: 123
Analysis run date: 2015-03-11 11:22:04 AM
Where the number in each column is the number of adverse events per treatment arm at the stated severity level.
Placebo
Body System or Organ Class
Treatment
Dictionary-Derived Term
Nervous System Disorders
Headache
General Disorders And Administration Site Conditions
Disease Progression
Gastrointestinal Disorders
Diarrhoea
Gastrointestinal Disorders
Nausea
Respiratory, Thoracic And Mediastinal Disorders Pulmonary Arterial Hypertension
Respiratory, Thoracic And Mediastinal Disorders Dyspnoea
Infections And Infestations
Upper Respiratory Tract Infection
Musculoskeletal And Connective Tissue Disorders
Pain In Jaw
General Disorders And Administration Site Conditions
Oedema Peripheral
Nervous System Disorders
Dizziness
Infections And Infestations
Nasopharyngitis
Musculoskeletal And Connective Tissue Disorders
Pain In Extremity
Gastrointestinal Disorders
Vomiting
Musculoskeletal And Connective Tissue Disorders
Myalgia
Respiratory, Thoracic And Mediastinal Disorders Cough
Musculoskeletal And Connective Tissue Disorders
Arthralgia
Cardiac Disorders
Right Ventricular Failure
Mild
Moderate
Severe
162
81
89
93
7
40
81
30
72
73
68
35
30
22
46
32
6
71
226
35
29
85
69
35
5
46
26
27
20
20
13
33
21
20
12
155
9
4
126
22
2
0
9
1
1
3
4
1
3
3
42
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
7
Not
Applicabl
e
0
3
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Mild
Moderate
Severe
306
52
206
146
8
43
69
129
46
74
82
63
59
64
47
28
5
256
163
126
99
43
48
29
49
36
30
21
62
74
46
18
49
17
82
130
31
15
86
20
4
7
6
3
0
15
10
9
0
4
31
Not
Applicabl
e
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Total
889
811
496
386
355
242
220
220
215
207
199
198
197
155
147
137
121
Project: Script Discovery and Acquisition Project Team
Working Group: Standard
Analyses and Code Sharing
Title: Screen Shots of the Displays Created by JumpStart Programs
Analysis 4: Serious Adverse Events by Severity and Arm
Serious Adverse Events by Organ Class and Term
NDA/BLA: 12345
Study: 123
Analysis run date: 2015-03-11 11:22:04 AM
Where subject count is the number of subjects in the treatment arm experiencing at least one serious adverse event per
organ class and term
Placebo
Body System or Organ Class
Dictionary-Derived Term
N=577
Subject
Count
Blood And Lymphatic System
Blood And Lymphatic System
Blood And Lymphatic System
Blood And Lymphatic System
Blood And Lymphatic System
Blood And Lymphatic System
Cardiac Disorders
Cardiac Disorders
Cardiac Disorders
Cardiac Disorders
Cardiac Disorders
Cardiac Disorders
Cardiac Disorders
Cardiac Disorders
Cardiac Disorders
Disorders
Disorders
Disorders
Disorders
Disorders
Disorders
Treatment
Anaemia
Haemorrhagic Anaemia
Idiopathic Thrombocytopenic Purpura
Leukopenia
Neutropenia
Thrombocytopenia
Right Ventricular Failure
Atrial Fibrillation
Atrial Flutter
Acute Right Ventricular Failure
Cardiac Arrest
Supraventricular Tachycardia
Cardio-Respiratory Arrest
Cardiogenic Shock
Cardiopulmonary Failure
3
0
0
0
1
0
42
4
4
5
4
4
2
2
1
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
8
Total
N=575
%
0.5
0.0
0.0
0.0
0.2
0.0
7.3
0.7
0.7
0.9
0.7
0.7
0.3
0.3
0.2
Subject
Count
5
1
1
1
0
1
34
7
4
2
2
1
2
2
3
N=1,152
%
0.9
0.2
0.2
0.2
0.0
0.2
5.9
1.2
0.7
0.3
0.3
0.2
0.3
0.3
0.5
Subject
Count
8
1
1
1
1
1
76
11
8
7
6
5
4
4
4
%
0.7
0.1
0.1
0.1
0.1
0.1
6.6
1.0
0.7
0.6
0.5
0.4
0.3
0.3
0.3
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
Analysis 5.1: Relative Risk
Placebo vs Treatment
Placebo
Body
System
Immun
Card
Metab
Metab
Gastr
Vasc
Infec
Infec
Musc
Skin
Blood
Card
Eye
Eye
Dictionary-Derived Term
Count
Hypersensitivity
9
Cyanosis
6
Fluid Overload
6
Gout
12
Gingival Bleeding
5
Hypertension
13
Otitis Externa
4
Viral Upper Respiratory Tract Infection
4
Systemic Sclerosis
4
Dermatitis Contact
4
Iron Deficiency Anaemia
15
Bundle Branch Block Right
3
Eye Pruritus
3
Ocular Hyperaemia
3
Treatment
%
1.6
1.0
1.0
2.1
0.9
2.3
0.7
0.7
0.7
0.7
2.6
0.5
0.5
0.5
Count
1
1
1
2
1
3
1
1
1
1
5
1
1
1
%
0.2
0.2
0.2
0.3
0.2
0.5
0.2
0.2
0.2
0.2
0.9
0.2
0.2
0.2
Relative
Risk
9.0
6.0
6.0
6.0
5.0
4.3
4.0
4.0
4.0
4.0
3.0
3.0
3.0
3.0
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
9
Lower
95% CI
( 1.1,
( 0.7,
( 0.7,
( 1.3,
( 0.6,
( 1.2,
( 0.4,
( 0.4,
( 0.4,
( 0.4,
( 1.1,
( 0.3,
( 0.3,
( 0.3,
Upper
95% CI
70.6)
49.5)
49.5)
26.6)
42.5)
15.1)
35.6)
35.6)
35.6)
35.6)
8.2)
28.7)
28.7)
28.7)
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
Analysis 5.2: Relative Risk and 95% Interval Analysis
Relative Risk and 95% Confidence Interval Analysis
Hypersensitivity
Cyanosis
Fluid Overload
Gout
Gingival Bleeding
Hypertension
Otitis Externa
Viral Upper Respiratory Tract…
Systemic Sclerosis
Dermatitis Contact
Iron Deficiency Anaemia
Bundle Branch Block Right
Eye Pruritus
Ocular Hyperaemia
Irritable Bowel Syndrome
Mouth Ulceration
Feeling Hot
Hyperthermia
Laryngitis
Onychomycosis
Animal Bite
Foot Fracture
Liver Function Test Abnormal
Hypercholesterolaemia
Arthritis
Breast Cancer
Sinus Headache
Interstitial Lung Disease
Dermatitis
Swelling Face
0
20
40
60
80
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
10
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
Analysis 6.1: Odds Ratio
Placebo vs Treatment
Placebo
Body
System
Immun
Metab
Card
Metab
Gastr
Vasc
Infec
Infec
Musc
Skin
Blood
Inv
Musc
Card
Dictionary-Derived Term
Count
Hypersensitivity
9
Gout
12
Cyanosis
6
Fluid Overload
6
Gingival Bleeding
5
Hypertension
13
Otitis Externa
4
Viral Upper Respiratory Tract Infection
4
Systemic Sclerosis
4
Dermatitis Contact
4
Iron Deficiency Anaemia
15
Liver Function Test Abnormal
6
Arthritis
6
Bundle Branch Block Right
3
Treatment
%
1.6
2.1
1.0
1.0
0.9
2.3
0.7
0.7
0.7
0.7
2.6
1.0
1.0
0.5
Count
1
2
1
1
1
3
1
1
1
1
5
2
2
1
%
0.2
0.3
0.2
0.2
0.2
0.5
0.2
0.2
0.2
0.2
0.9
0.3
0.3
0.2
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
11
Odds
Ratio
9.1
6.1
6.0
6.0
5.0
4.4
4.0
4.0
4.0
4.0
3.0
3.0
3.0
3.0
Lower
95% CI
( 1.3,
( 1.3,
( 0.7,
( 0.7,
( 0.6,
( 1.2,
( 0.4,
( 0.4,
( 0.4,
( 0.4,
( 1.0,
( 0.5,
( 0.5,
( 0.2,
Upper
95% CI
399.3)
56.2)
277.9)
277.9)
237.7)
24.1)
197.7)
197.7)
197.7)
197.7)
10.8)
30.6)
30.6)
157.8)
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
Analysis 6.2: Odds Ratio and 95% Interval Analysis
Odds Ratio and 95% Confidence Interval Analysis
Hypersensitivity
Gout
Cyanosis
Fluid Overload
Gingival Bleeding
Hypertension
Otitis Externa
Viral Upper Respiratory Tract…
Systemic Sclerosis
Dermatitis Contact
Iron Deficiency Anaemia
Liver Function Test Abnormal
Arthritis
Bundle Branch Block Right
Eye Pruritus
Ocular Hyperaemia
Irritable Bowel Syndrome
Mouth Ulceration
Feeling Hot
Hyperthermia
Laryngitis
Onychomycosis
Animal Bite
Foot Fracture
Hypercholesterolaemia
Breast Cancer
Sinus Headache
Interstitial Lung Disease
Dermatitis
Swelling Face
0
2
4
6
8
10
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
12
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
8.2. AE Toxicity
Analysis 1: Toxicity Grade Summary
Toxicity Grade Summary
NDA/BLA: 12345
Study: 123
Analysis run date: 2015-01-16 2:06:12 PM
Where subject count is the number of subjects experiencing at least one adverse event at the stated toxicity grade using the maximum
toxicity grade per subject
Treatment
N=254
All Grades
Subject
Count
Total
251
Control
N=239
Grades 3/4/5
Subject
Count
%
98.8
172
%
67.7
All Grades
Subject
Count
233
Grades 3/4/5
%
97.5
Subject
Count
144
%
60.3
NOTES:
1 This analysis uses the safety population and only counts adverse events that start between a subject's first exposure and 30 days after the
subject's last exposure
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
13
Project: Script Discovery and Acquisition Project Team
Working Group: Standard
Analyses and Code Sharing
Title: Screen Shots of the Displays Created by JumpStart Programs
Analysis 2: Preferred Term Analysis by Toxicity Grade (V1)
Preferred Term Analysis by Toxicity Grade
NDA/BLA: 12345
Study: 123
Analysis run date: 2015-01-16 2:06:12 PM
Where subject count is the number of subjects experiencing at least one adverse event at the stated toxicity grade using the maximum
toxicity grade per subject, organ class, and term
Treatment
N=254
Body System or Organ Class
Dictionary-Derived Term
All Grades
Subject
Count
Blood And Lymphatic System
Blood And Lymphatic System
Blood And Lymphatic System
Blood And Lymphatic System
Blood And Lymphatic System
Blood And Lymphatic System
Blood And Lymphatic System
Blood And Lymphatic System
Blood And Lymphatic System
Blood And Lymphatic System
Blood And Lymphatic System
Blood And Lymphatic System
Cardiac Disorders
Cardiac Disorders
Disorders
Disorders
Disorders
Disorders
Disorders
Disorders
Disorders
Disorders
Disorders
Disorders
Disorders
Disorders
Anaemia
Eosinophilia
Iron Deficiency Anaemia
Leukocytosis
Leukopenia
Lymphadenopathy
Lymphoid Tissue Hyperplasia
Lymphopenia
Microcytic Anaemia
Neutropenia
Normochromic Normocytic Anaemia
Thrombocytopenia
Acute Coronary Syndrome
Angina Pectoris
27
1
1
1
1
1
0
5
0
1
2
9
1
3
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
14
Control
N=239
Grades 3/4/5
%
10.6
0.4
0.4
0.4
0.4
0.4
0.0
2.0
0.0
0.4
0.8
3.5
0.4
1.2
Subject
Count
4
0
0
0
0
0
0
0
0
0
0
1
1
0
%
1.6
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.4
0.4
0.0
All Grades
Subject
Count
17
1
0
0
2
2
1
4
1
4
1
3
0
0
Grades 3/4/5
%
7.1
0.4
0.0
0.0
0.8
0.8
0.4
1.7
0.4
1.7
0.4
1.3
0.0
0.0
Subject
Count
4
0
0
0
0
0
0
2
0
3
0
0
0
0
%
1.7
0.0
0.0
0.0
0.0
0.0
0.0
0.8
0.0
1.3
0.0
0.0
0.0
0.0
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
Analysis 3: Preferred Term Analysis by Toxicity Grade (V2)
Preferred Term Analysis by Toxicity Grade
NDA/BLA: 12345
Study: 123
Analysis run date: 2015-01-16 2:06:12 PM
Where subject count is the number of subjects experiencing at least one adverse event at the stated toxicity grade using
the maximum toxicity grade per subject, organ class, and term
Treatment
N=254
Adverse Event
All Grades
Subject
Count
%
Control
N=239
Grades 3/4/5
Subject
Count
%
All Grades
Subject
Count
%
Grades 3/4/5
Subject
Count
%
Blood And Lymphatic System Disorders
Anaemia
Eosinophilia
Iron Deficiency Anaemia
Leukocytosis
Leukopenia
Lymphadenopathy
Lymphoid Tissue Hyperplasia
Lymphopenia
Microcytic Anaemia
Neutropenia
Normochromic Normocytic Anaemia
Thrombocytopenia
27
1
1
1
1
1
0
5
0
1
2
9
10.6
0.4
0.4
0.4
0.4
0.4
0.0
2.0
0.0
0.4
0.8
3.5
4
0
0
0
0
0
0
0
0
0
0
1
1.6
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.4
17
1
0
0
2
2
1
4
1
4
1
3
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
15
7.1
0.4
0.0
0.0
0.8
0.8
0.4
1.7
0.4
1.7
0.4
1.3
4
0
0
0
0
0
0
2
0
3
0
0
1.7
0.0
0.0
0.0
0.0
0.0
0.0
0.8
0.0
1.3
0.0
0.0
Project: Script Discovery and Acquisition Project Team
Working Group: Standard
Analyses and Code Sharing
Title: Screen Shots of the Displays Created by JumpStart Programs
Analysis 4: Two-Term MedDRA Analysis (V1)
Adverse Events Two-Term MedDRA Analysis
by System Organ Class and Preferred Term
NDA/BLA: 12345
Study: 123
Analysis run date: 2015-01-16 2:06:12 PM
Where subject count is the number of subjects experiencing at least one adverse event at the stated toxicity grade using the maximum
toxicity grade per subject, system organ class, and preferred term
Treatment
N=254
System Organ Class
Control
N=239
Preferred Term
All Grades
Subject
Count
Blood and lymphatic system
Blood and lymphatic system
Blood and lymphatic system
Blood and lymphatic system
Blood and lymphatic system
Blood and lymphatic system
Blood and lymphatic system
Blood and lymphatic system
Blood and lymphatic system
Blood and lymphatic system
Blood and lymphatic system
Blood and lymphatic system
disorders
disorders
disorders
disorders
disorders
disorders
disorders
disorders
disorders
disorders
disorders
disorders
Risk Difference
Anaemia
Eosinophilia
Iron deficiency anaemia
Leukocytosis
Leukopenia
Lymphadenopathy
Lymphoid tissue hyperplasia
Lymphopenia
Microcytic anaemia
Neutropenia
Normochromic normocytic anaemia
Thrombocytopenia
27
1
1
1
1
1
0
5
0
1
2
9
%
% Lower
CL
10.6
0.4
0.4
0.4
0.4
0.4
0.0
2.0
0.0
0.4
0.8
3.5
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
16
(7.12,
(0.01,
(0.01,
(0.01,
(0.01,
(0.01,
(0.00,
(0.64,
(0.00,
(0.01,
(0.10,
(1.63,
All Grades
% Upper
CL
15.09)
2.17)
2.17)
2.17)
2.17)
2.17)
1.44)
4.53)
1.44)
2.17)
2.82)
6.62)
Subject
Count
17
1
0
0
2
2
1
4
1
4
1
3
%
7.1
0.4
0.0
0.0
0.8
0.8
0.4
1.7
0.4
1.7
0.4
1.3
% Lower
CL
(4.20,
(0.01,
(0.00,
(0.00,
(0.10,
(0.10,
(0.01,
(0.46,
(0.01,
(0.46,
(0.01,
(0.26,
% Upper
CL
11.14)
2.31)
1.53)
1.53)
2.99)
2.99)
2.31)
4.23)
2.31)
4.23)
2.31)
3.62)
Risk
Difference
3.5
0.0
0.4
0.4
-0.4
-0.4
-0.4
0.3
-0.4
-1.3
0.4
2.3
Confidence Interval
Lower
CL
(-1.48,
(-1.15,
(-0.38,
(-0.38,
(-1.83,
(-1.83,
(-1.24,
(-2.06,
(-1.24,
(-3.08,
(-0.99,
(-0.39,
Upper
CL
8.52)
1.10)
1.16)
1.16)
0.94)
0.94)
0.40)
2.65)
0.40)
0.52)
1.73)
4.96)
Project: Script Discovery and Acquisition Project Team
Working Group: Standard
Analyses and Code Sharing
Title: Screen Shots of the Displays Created by JumpStart Programs
Analysis 5: Two-Term MedDRA Analysis
Adverse Events Two-Term MedDRA Analysis
by System Organ Class and Preferred Term; Sorted by Relative Risk
NDA/BLA: 12345
Study: 123
Analysis run date: 2015-01-16 2:06:12 PM
Where subject count is the number of subjects experiencing at least one adverse event at the stated toxicity grade using the maximum
toxicity grade per subject, system organ class, and preferred term
Treatment
N=254
Control
N=239
All Grades
All Grades
Risk Difference
Relative Risk
Odds Ratio
Adverse Event
P-value
Subject
Count
%
%
Lower CL
%
Upper CL
Subject
Count
%
%
Lower CL
%
Upper CL
Confidence Interval
Risk
Difference Lower CL Upper CL
Relative
Risk
Confidence Interval
Lower CL
Upper CL
Odds
Ratio
Confidence Interval
Lower CL
Upper CL
Eye disorders
Retinal detachment
Chorioretinopathy
Visual impairment
Macular oedema
Detachment of retinal pigment epithelium
Vitreous floaters
Age-related macular degeneration
Diplopia
Orbital oedema
Retinopathy
21
30
7
4
8
6
2
2
2
2
8.3
11.8
2.8
1.6
3.1
2.4
0.8
0.8
0.8
0.8
(5.19,
(8.11,
(1.12,
(0.43,
(1.37,
(0.87,
(0.10,
(0.10,
(0.10,
(0.10,
12.36)
16.43)
5.60)
3.98)
6.11)
5.07)
2.82)
2.82)
2.82)
2.82)
0
1
0
0
1
1
0
0
0
0
0.0
0.4
0.0
0.0
0.4
0.4
0.0
0.0
0.0
0.0
(0.00,
(0.01,
(0.00,
(0.00,
(0.01,
(0.01,
(0.00,
(0.00,
(0.00,
(0.00,
1.53)
2.31)
1.53)
1.53)
2.31)
2.31)
1.53)
1.53)
1.53)
1.53)
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
17
8.3
11.4
2.8
1.6
2.7
1.9
0.8
0.8
0.8
0.8
(4.88,
(7.34,
(0.74,
(0.04,
(0.43,
(-0.10,
(-0.30,
(-0.30,
(-0.30,
(-0.30,
11.65)
15.45)
4.77)
3.11)
5.03)
3.98)
1.87)
1.87)
1.87)
1.87)
40.5*
28.2
14.1*
8.5*
7.5
5.6
4.7*
4.7*
4.7*
4.7*
(2.47,
(3.88,
(0.81,
(0.46,
(0.95,
(0.68,
(0.23,
(0.23,
(0.23,
(0.23,
664.40)
205.38)
245.85)
156.49)
59.73)
46.55)
97.52)
97.52)
97.52)
97.52)
44.1*
31.9
14.5*
8.6*
7.7
5.8
4.7*
4.7*
4.7*
4.7*
(2.66,
(5.19,
(0.82,
(0.46,
(1.02,
(0.69,
(0.23,
(0.23,
(0.23,
(0.23,
732.32)
1305.76)
255.55)
160.68)
344.85)
265.95)
99.29)
99.29)
99.29)
99.29)
0.00
0.00
0.02
0.12
0.04
0.12
0.50
0.50
0.50
0.50
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
8.3. Demographics
Analysis 1: Overview
Demographic Baseline Characteristics: Overview
NDA12345
Study: 123
Analysis run date: 2015-03-03 8:21:03 AM
Demographic Baseline Characteristics
Age
Mean (SE)
Min
Q1
Median
Q3
Max
Age Group
Age under 50 years
Age 50 and over
F
M
Asian
Black Or African American
Hispanic
White
Other
Missing
Sex
Race
Ethnicity
Placebo
Treatment
Overall
N=582
47.9 (15.6)
18
35
49
60
80
Count
%
305
52.4
277
47.6
466
80.1
116
19.9
120
20.6
14
2.4
63
10.8
375
64.4
10
1.7
582
100.0
N=574
48.2 (15.2)
18
37
49
61
78
Count
%
301
52.4
273
47.6
457
79.6
117
20.4
125
21.8
13
2.3
51
8.9
376
65.5
9
1.6
574
100.0
N=1156
48.1 (15.4)
18
36
49
61
80
Count
%
606
52.4
550
47.6
923
79.8
233
20.2
245
21.2
27
2.3
114
9.9
751
65.0
19
1.6
1156
100.0
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
18
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
Analysis 2: Age Groups
Demographic Baseline Characteristics: Age Groups
NDA12345
Study: 123
Analysis run date: 2015-03-03 8:21:03 AM
Placebo
Treatment
Overall
Age Group
N=582
Age under 50 years
Age 50 and over
Count
305
277
N=574
%
52.4
47.6
Count
301
273
N=1156
%
52.4
47.6
Count
606
550
Age Groups
100
90
80
Percentage (%)
70
60
50
40
30
20
10
0
Age under 50 years
Age 50 and over
Placebo
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
19
%
52.4
47.6
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
Analysis 3: Age Groups by Disposition
Demographic Baseline Characteristics by Disposition Term: Age Groups
NDA12345
Study: 123
Analysis run date: 2015-03-03 8:21:03 AM
The Count column shows the count of subjects in each demographic group per arm whose last disposition event is the disposition term shown.
See the front page for further information. The % column shows the proportion of the demographic group in each arm that the count represents.
Placebo
Standard Disposition Term
Treatment
N=582
Completed
Death
Unknown
Overall
Age Group
Count
241
208
49
56
14
13
Age under 50 years
Age 50 and over
Age under 50 years
Age 50 and over
Age under 50 years
Age 50 and over
N=574
%
79.0
75.1
16.1
20.2
4.6
4.7
Count
249
201
43
57
9
15
N=1156
%
82.7
73.6
14.3
20.9
3.0
5.5
Count
490
409
92
113
23
28
Analysis 4.1: Age Statistics - Table
Demographic Baseline Characteristics: Age Statistics
NDA12345
Study: 123
Analysis run date: 2015-03-03 8:21:03 AM
Age Statistic
Mean (SE)
Mode
Min
Q1
Median
Q3
Max
Placebo
Treatment
Overall
N=582
47.9 (15.6)
36
18
35
49
60
80
N=574
48.2 (15.2)
40
18
37
49
61
78
N=1156
48.1 (15.4)
54
18
36
49
61
80
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
20
%
80.9
74.4
15.2
20.5
3.8
5.1
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
Analysis 4.2: Age Statistics - Figure
Ages
Age Statistics
90
80
70
60
50
40
30
20
10
0
11
14
12
12
12
13
35
37
36
Placebo
Treatment
Treatment Arms
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
21
Overall
Project: Script Discovery and Acquisition Project Team
Working Group: Standard
Analyses and Code Sharing
Title: Screen Shots of the Displays Created by JumpStart Programs
Analysis 5: Country and Site ID
Demographic Baseline Characteristics: Country and Site ID
NDA12345
Study: 123
Analysis run date: 2015-03-03 8:21:03 AM
Placebo
Country
Treatment
N=582
ARG
AUS
Overall
Site ID
6004
6005
6001
6006
6008
6007
1002
1004
1005
1008
1001
1007
1003
1006
1009
Count
3
3
4
2
1
1
8
6
5
4
3
2
1
2
1
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
22
N=574
%
0.5
0.5
0.7
0.3
0.2
0.2
1.4
1.0
0.9
0.7
0.5
0.3
0.2
0.3
0.2
Count
3
3
2
1
1
0
8
6
4
3
4
2
2
1
0
N=1156
%
0.5
0.5
0.3
0.2
0.2
0.0
1.4
1.0
0.7
0.5
0.7
0.3
0.3
0.2
0.0
Count
6
6
6
3
2
1
16
12
9
7
7
4
3
3
1
%
0.5
0.5
0.5
0.3
0.2
0.1
1.4
1.0
0.8
0.6
0.6
0.3
0.3
0.3
0.1
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
8.4. Disposition
Analysis 1: Disposition Events by Arm for All Subjects
206192
Disposition Events by Arm for All Subjects
NDA12345
Study: 123
Analysis run date: 2015-01-05 11:59:07 AM
Category
of Disposition Event
Subcategory
of Disposition Event
Protocol Milestone
Protocol
Sample Collection Milestone Rcr
Disposition Event
Placebo Discontinuation
Protocol
Disposition Event
Randomization
Informed Consent Obtained
All Eligibility Criteria Met
Not All Eligibility Criteria Met
Informed Consent Obtained
Informed Consent Not Obtained
Progression Of Disease
Adverse Event
Withdrawal By Subject
Physician Decision
Death
Other
Non-Compliance With Study Drug
Non-Compliance
Lost To Follow-Up
Treatment
Subject
Count
%
254
100.0
254
100.0
241
94.9
13
5.1
199
78.3
54
21.3
75
29.5
38
15.0
2
0.8
3
1.2
2
0.8
0
0.0
1
0.4
2
0.8
0
0.0
Control
Subject
Count
239
239
226
13
187
52
129
20
2
1
1
2
1
0
1
%
100.0
100.0
94.6
5.4
78.2
21.8
54.0
8.4
0.8
0.4
0.4
0.8
0.4
0.0
0.4
Treatment
Subject
Count
%
254
100.0
254
100.0
241
94.9
13
5.1
199
78.3
54
21.3
75
29.5
38
15.0
2
0.8
3
1.2
2
0.8
0
0.0
1
0.4
2
0.8
Control
Subject
Count
239
239
226
13
187
52
129
20
2
1
1
2
1
0
%
100.0
100.0
94.6
5.4
78.2
21.8
54.0
8.4
0.8
0.4
0.4
0.8
0.4
0.0
Analysis 2: Disposition Events by Arm for Exposed Subjects
206192
Disposition Events by Arm for Exposed Subjects
NDA12345
Study: 123
Analysis run date: 2015-01-05 11:59:07 AM
Category
of Disposition Event
Protocol Milestone
Subcategory
of Disposition Event
Missing
Protocol
Sample Collection Milestone Rcr
Disposition Event
Placebo Discontinuation
Disposition Event
Randomization
Informed Consent Obtained
All Eligibility Criteria Met
Not All Eligibility Criteria Met
Informed Consent Obtained
Informed Consent Not Obtained
Progression Of Disease
Adverse Event
Withdrawal By Subject
Physician Decision
Death
Other
Non-Compliance With Study Drug
Non-Compliance
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
23
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
Analysis 3: Time to Disposition Event by Arm for All Subjects
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
24
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
Analysis 4: Time to Disposition Event by Arm for Exposed Subjects
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
25
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
8.5. Exposure
Analysis 1: Total Number of Days of Drug
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
26
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
Analysis 2: Cumulative Dose
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
27
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
Analysis 3: Dose Descriptive Statistics and Boxplot of Doses by Arm
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
28
Project: Script Discovery and Acquisition Project Team
Title: Screen Shots of the Displays Created by JumpStart Programs
Analysis 4: Count of Subjects by Treatment Arm and Actual Treatment
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
29
Working Group: Standard
Analyses and Code Sharing
Project: Script Discovery and Acquisition Project Team
Title: Screen Shots of the Displays Created by JumpStart Programs
Analysis 5: Dose Changes during the Study
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
30
Working Group: Standard
Analyses and Code Sharing
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
8.6. Liver
Analysis 1: Liver Lab Tests Greater Than Upper Limit of Normal
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
31
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
Analysis 2.1: Combinations for Possible Hy’s Law Cases at the Same Visit
Analysis 2.2: Combinations for Possible Hy’s Law Cases at Any Time during the
Study
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
32
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
Analysis 2.3: Combinations for Possible Hy’s Law Cases Patients at Any Time
during the Study
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
33
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
Analysis 3: Baseline Lab Tests – Maximum vs Baseline
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
34
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
Analysis 4: Maximum AST/ALT vs Maximum TB Lab Test Results per Subject
Charts
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
35
Project: Script Discovery and Acquisition Project Team
Working Group:
Standard Analyses and
Title: Screen Shots of the Displays Created by JumpStart
Code Sharing
Programs
Analysis 5: Maximum Lab Test Results per Subject by Study Day
Script Discovery and Acquisition Project Team – Version 1.0 – 2017-Mar-17
36